Project Summary/Abstract Human vision starts when photoreceptors collect and respond to light. Photoreceptors do not function in isolation though, but share close interdependence with neighboring photoreceptors, retinal pigment epithelium (RPE) cells, and choriocapillaris (CC). These close interactions underlie normal function of photoreceptors, but also the entire photoreceptor-RPE-CC complex, the primary site of most retinal dystrophies including age-related macular degeneration (AMD) and inherited diseases such as retinitis pigmentosa (RP). Techniques to assess this complex in vivo, however, are limited. New optical modalities that are rapid, specific, and non-invasive hold the promise of greatly expanding our capability to monitor more accurately and completely the photoreceptor-RPE-CC complex. This study takes advantage of unique AO and OCT instrumentation developed in my laboratory for sampling rapidly and reproducibly volume regions of the photoreceptor-RPE-CC complex at the cellular level. We will use MHz AO-OCT in conjunction with sub-cellular 3D registration and phase techniques that we have developed that are sensitive to optical length changes as small as 45 nm. We will use these techniques to investigate three specific aims: (1) determine properties of photoreceptor disc shedding, (2) evaluate disruption in the cellular surround of drusen, an early indicator of AMD, and (3) measure cell loss dynamics in RP.